A 3D model of a human epiblast reveals BMP4-driven symmetry breaking.
Nat Cell Biol
; 21(7): 900-910, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31263269
Breaking the anterior-posterior symmetry in mammals occurs at gastrulation. Much of the signalling network underlying this process has been elucidated in the mouse; however, there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro three-dimensional model of a human epiblast whose size, cell polarity and gene expression are similar to a day 10 human epiblast. A defined dose of BMP4 spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial-to-mesenchymal transition. We show that WNT signalling and its inhibitor DKK1 play key roles in this process downstream of BMP4. Our work demonstrates that a model human epiblast can break axial symmetry despite the absence of asymmetry in the initial signal and of extra-embryonic tissues or maternal cues. Our three-dimensional model is an assay for the molecular events underlying human axial symmetry breaking.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica no Desenvolvimento
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Técnicas de Cultura de Tecidos
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Linha Primitiva
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Proteína Morfogenética Óssea 4
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Camadas Germinativas
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article